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First published online October 14, 2004

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Notch signalling: shedding light into the pit

Endocytosis is extremely important for the activity of the developmentally crucial Notch signalling pathway. Upon binding to transmembrane ligands of the Delta/Serrate/Lag2 (DSL) family, the cell-surface receptor Notch is cleaved, allowing its cytosolic domain to enter the nucleus and activate target genes. Notch activation also seems to require DSL ligand endocytosis. Two groups now shed further light on this process and one reaches some surprising conclusions. On p. 5355, Overstreet et al. show that Delta signalling in the developing Drosophila eye requires the activity of Liquid facets (Lqf), the Drosophila homologue of epsin, an adaptor protein involved in clathrin-mediated endocytosis. They also show that in one Notch signalling event in the eye, Delta internalisation and signalling is promoted by Fat facets (Faf), which deubiquitinates Lqf, and by Neuralised (Neur), which ubiquitinates Delta. On p. 5367, Wang and Struhl report that Lqf is required for cells to send, but not to receive, DSL signals and that internalisation of DSL signals may be the sole role of epsin in Drosophila. They show that mono-ubiquitination of DSL proteins by Neur allows Lqf to target DSL proteins to a special endocytic pathway that they must enter to signal. Both groups report that the bulk endocytosis of DSL proteins does not require Lqf, leading Wang and Struhl to propose that Lqf targets DSL proteins to a subclass of coated pits required for Notch activation or to an endocytic recycling pathway that converts DSL proteins into active ligands.

Related articles in Development:

Fat facets and Liquid facets promote Delta endocytosis and Delta signaling in the signaling cells

Erin Overstreet, Erin Fitch, and Janice A. Fischer
Development 2004 131: 5355-5366. [Abstract] [Full Text]  

Drosophila Epsin mediates a select endocytic pathway that DSL ligands must enter to activate Notch

Weidong Wang and Gary Struhl
Development 2004 131: 5367-5380. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content